Despite great advances in our knowledge of bone, bone cells, and bone metabolism, our understanding of the mechanisms by which the skeleton contributes to calcium homeostasis remains primitive and incomplete. Yet, detailed information on this problem is prerequisite to an understanding of calcium regulation as a whole and to a rational approach to such unsolved clinical problems such as osteoporosis to name just one. It is the purpose of this research to employ model systems to identify and characterize the cellular and hormonal mechanisms controlling the ion fluxes, of calcium and phosphate especially, to and from the skeleton. Using techniques recently developed for the quantitation of ion influxes and effluxes, in isolated calvaria in vitro, the effects of physiological agents and stresses will be studied. The observed changes will be correlated with the metabolic and physical status of bone tissue itself. Aerobic glycolysis, fatty acid oxidation, oxygen consumption, changes in specific cell populations, the permeability of intercellular matrix and the presence and amounts of specific regulatory proteins will be among the variables used in this correlation.